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[Extraction of ephedrine/pseudoephedrine from pills]
[This pill extraction method is depreciated as the pill formulas has changed since]
[Oxidizing of Ephedrine or Pseudoephedrine to Methcathinone]
Now you have your purified "feed stock". If everything was done as stated above, it WILL be pure and clean enough for the next oxidation step. If not, then you're going to have a lower yield due to the using up of your oxidant by something that is soluble in the Colman's Camper Fuel. I don't know what that something is, but with proper clean-up, it can be removed.
For every gram of feed stock, use 10 mL of distilled water. Experience has shown that the water from the water mills works just fine, but I wouldn't take the chance as there is no guarantee that something in the water will not fuck-up your reaction. Tap-water is an absolute NO-NO!
Dissolve your "feed stock" in the water. This will not occur as fast as you might think. A little agitation or stirring is called for. Now weigh out separately 3 grams of potassium dichromate for every 5 grams of "feed stock" used. You'll have to figure out what amount of potassium dichromate is needed for the reaction and then determine the amount of sulfuric acid (the OTC drain cleaning kind is okay) needed in the reaction which is calculated as follows: Use 3 mL of sulfuric acid to every gram of potassium dichromate used. After measuring out the sulfuric acid, add it slowly to the "feed stock solution. Cooling down the "feed stock" solution before this addition might increase yields but who knows. Swirl the now formed aqueous sulfate salt of the "feed stock" by hand. The solution will get somewhat hot but will not go above 50°C (at least, it should not). Cool the mixture down to room temperature. Now you have a solution of "feed stock" sulfate in dilute sulfuric acid. This step is important because if one adds already formed chromic acid solution to a solution of the hydrochloride salt of "feed stock" one gets a strange precipition that eventually redissolves but almost always spells low yields at the end of the synthesis. Not good. Anyway, after the solution cools, add the required previously calculated amount of potassium dichromate and begin magnetic stirring. This reaction is not exothermic so there is no need for thermal control. It will take a little while for the potassium dichromate to dissolve but eventually it will. At first, the solution is light orange and somewhat transparant. In about an hour to two hours, however, the potassium dichromate will have dissolved into an opaque dark-reddish-orange solution. Allow the solution to stir undisturbed for 12 hours. The stirring can go up to 24 hours without a significant reduction in yield, but by no means must the reaction be halted before 8 hours. Whatever the reaction vessel used, the lid should not be tightly closed as some gasses (harmless) sometimes form.
At the end of the reaction period the solution should look very much like when it first became dark with just a hint of green thrown in. Usually, the color of the solution can best be guaged by using a source of light to enhance the outer edge of the solution, which will more clearly indicate the hue of the mixture. If the solution has any uniform purple quality, then the original "feed stock" was tainted (not purified enough) meaning that there might be low yields of product. At this point, measure out a capful of IPA (isopropyl alcohol; rubbing alcohol; 50%,70%, 91% all are okay) and add this to the solution and allow to stir for about ten minutes. This step is paramount as it will ensure that all the oxidant is reduced and that no chromium sludge will form at the point of basification. The solution might get slightly hot during this period but this is no big deal. While the mixture is stirring, measure out 7.5 grams of NaOH (Lye) for every gram of potassium dichromate used. Dissolve this in enough distilled water (placed in a beaker or measuring cup surrounded by an ice bath) to make a 25% solution. The beaker must FIRST be nestled in the ice bath BEFORE the addition of the Lye or else the beaker will crack from thermal shock. After the NaOH solution has cooled, add more ice to the bath and allow it to cool for 20 minutes more. At this point, set-up another ice-bath. Stop the stirring of the vessel containing the solution of desired product. It should now be either a uniform opaque marine blue color or an opaque forest green color (this varies but both look very pretty). Place the vessel in the second ice bath and cool for 20 minutes as well. Once both the NaOH and product solutions have cooled down for the required time, get a large 3 gallon pickle jar (empty and clean) and transfer the contents of the product vessel into it. Pour into this solution an equal volume of toluene which will float on top of the product aqueous solution. Fill up the kitchen sink with water and a bag of ice. The requirement here is only that the toluene/product solution can easily be immersed beneath the ice-bath. Put on gloves (as the water is very cold) and quickly pour the NaOH solution into the pickle jar. IMMEDIATELY cap and seal and begin to aggitate the jar by hand to allow both layers of toluene and product solution to mix vigorously and in all proportions. Do this for about one minute WHILE UNDER THE ICE BATH and then hold under the ice bath until both layers separate. Hold the jar steady as it will float in the ice-bath and possibly tip over spilling its contents. Bee careful. After the layers have separated, remove the jar from the ice bath. What should be visible is the toluene layer (possibly somewhat cloudy) floating above a beautiful opaque forest green solution with NO CHROMIUM SLUDGE FORMATION WHATSOEVER!!!!!. Separate the layers and wash the toluene layer with distilled water. What should happen here is as follows: The toluene layer should immediately grow cloudy and should separate from the water layer rather quickly (1 to 2 minutes). If separation does not occur rapidly, then some unreacted feed stock is still present. This is not a problem but to make separation a quicker easier task, add a little table salt (NaCl) to salt out the toluene layer. Wash three times. With each wash, the water layer will grow more and more clear, until it just simply looks like plain water. The toluene layer will now be cloudy. Dry with anhydrous magnesium salts. This will get rid of the cloudiness. Bubble with HCl gas. The crystals of product will - unlike the crystals of "feed stock" - form in little strings which will cling to the sides of the flask.
After gassing until there are no more crystals formed, there should be either clean crystals clinging to the sides of the flask or alot of syrupy goo instead. Either of these will yield the desired product. So next, decant the toluene from the crystals and add about 500 mL of acetone. Start mixing with a stainless steel or PVC plastic spoon, scraping the sides, etc. etc. Eventually, the acetone will dissolve the gunk and the crystals will form. After a while there will be either a clear or yellowish acetone solution with a goodly amount of crystalline product floating at the bottom of the beaker. Vacuum filter these crystals, squeeze the acetone out of the coffee filters as described earlier and then set the filter paper along with the product out to dry. Chopping the product under a lamp speeds up this process. Next, once the dried product is obtained, transfer all of it to a 500 mL flat-bottomed flask and set up for reflux and stir and heat the mixture for about 30 minutes. By the completion of this time period, all of the pyrazine contaminant (for more information, refer to other relevant threads of mine) should have been removed by the acetone wash. Filter while hot, squeeze, and set to dry. Yield is about 35-50% of VERY clean and VERY pure product. Does not burn when inhaled, and has a very bitter but tolerable taste. Enjoy.
Here is the Jones Oxidation method I posted in ADC. My Grandma tried it, and found no flaw. You guys can tell me if there are typos or any problems with it. It is the best oxidation process for secondary alcohols that I know of. It even has been used on Codeine (a tert alcohol) with limited success. OK, here it is:
Part 1 - Some Boring(?) Chemistry
'Reduction' is the addition of hydrogen to a molecule, and 'oxidation' is the removal of hydrogen. The pseudo or ephedrine that we are starting with is our 'substrate'. Our first task will be to oxidize the 'OH' (hydroxyl group) to 'O'. To remove the unwanted hydrogen, we will use a powerful oxidizing solution, known as 'Jones Reagant'.
Jones reagent is prepared by dissolving 26.72 grams of chromium trioxide (CrO3) in 23ml of concentrated sulfuric acid, and then diluting the mixture to 100ml with water. One mL of the reagant oxidizes 4 'millimoles' of an alcohol. Secondary alcohols (like we have) are oxidized to ketones in excellent yields.
A 'mole' is very large number of molecules (6x1023). The actual number is not important, what is important is that a mole of one substance contains the exact same number of molecules as a mole of any other. A mole of lead weighs 207.2 grams, and its molecular weight is 207.2. A mole of ibuprofen weighs 206.28 grams, mw=206.28. A mole of pseudoephedrine (mw=165.23) weighs 165.23 grams. So if I choose to start with 2 grams of pseudoephedrine, (or 2 x 1/165.23 moles = .0121 moles = 12.1 millimoles), and each mL of the jones reagant oxides 4 millimoles, I will need 12.1 / 4mL of Jones reagant, or 3.03 mL. I will prepare exactly 4mL of the reagent, since I am bound to lose a small amount in the glassware and on the table!
So we only need 4/100 of the 26.72 grams of CrO3 (chromium trioxide) and 23ml H2SO4 (sulfuric acid) to make our needed 4mL of reagent. Half molar amounts of sodium dichromate, potassium dichromate or ammonium dichromate may be substituted. This is because each molecule of CrO3 (mw=99.994) has one chromium atom in the +6 state (that is with 6 bonds, 2 to each of 3 oxygens). Each molecule of sodium dichromate - Na2Cr2O7·2H2O (mw 298) has 2 chromiums in the +6 state (and the chromium is our oxidant in this case). In this example the 1.068 (4/100 x 26.72) grams of CrO3 = 1.068/99.994 or 10.68 millimoles. 10.68/2 mmoles is needed of sodium dichromate. So 5.34 mmoles = 298 x 0.00534 = 1.59 grams. So 1.59 grams of sodium dichromate may be used in place of 1.068 grams of CrO3 (chromium trioxide).
Part 2 - Oxidizing the Alcohol to a Ketone
Lets get to work. 1.068 grams (I used just over 1 gram) CrO3 are added to 0.92ml H2SO4, and distilled water is added to bring the total volume to 4ml. 2 grams of pseudoephedrine are dissolved in 20ml acetone, and cooled in an ice bath. The Jones reagant is slowly added to the pseudoephedrine, dropwise and with stirring. The mixture becomes a reddish brown.
Since we used just about the exact number of molecules required, and under very mild conditions, the reaction will proceed slowly, but very smoothly. Just let the ice melt and the stirred solution warm over night.
Part 3 - Extracting the Ketone
About 12-18 hours later the reaction is complete, the color is now a very dark green. We now have to neutarlize and extract our ketone. Add about 20mL of water, and chill in an ice bath. Dropwise and with stirring add about 1 gram of lye (Sodium Hydroxide - NaOH) in a solution with as little water as possible (highly concentrated). Check the pH regularly, and stop at pH=12. The now basic solution is shaken with 50ml of toluene. Allow to stand and two layers will form. The ketone will move into the toluene layer. Let the mix settle and remove the acetone/toluene/ketone and put it aside. Add another 50mL portion of toluene to the aqueous (water-based) portion, shake, filter (which breaks the emulsion and removes some chromium salts), and remove and put aside the toluene. Ensure that pH is still 12, and repeat again with another 50mL portion of toluene.
Combine the three toluene extractions and evaporate them with a hair dryer. The result is the impure ketone of pseudoephedrine, also know as methcathinione or ephedrone.
We used very gentle oxidation, neutralization, extraction, and evaporation conditions. Shortcuts can be used (no ice, evaporate with some heat, etc.), but good lab practice is never to stress the substrate needlessly. So we were careful.
The raw "dirty" methcathinone weighs about 1.7 grams
It is purified by adding just enough tolene to redissolve it. Some particles will not dissolve, and are left in the drying dish. The toluene is filtered to remove any additional particles, poured back into the separation funnel and shaken with an equal amount of distilled water. This removes any small amount of water solubles. The toluene is put into a clean dish and dried once again. The impurities are more soluble in acetone than the ephedrone, so a very small amout of acetone is added, and sloshed around. Pour this off into the waste (original green mix). What's left is a little over 1 gram (about 60% yield) of relatively pure, slightly off-white methcathinone.
Better chemists can expect a much higher yield. This is a general procedure. The example given - Pseudoephedrine or Ephedrine to Methcatinone - is for illustrative purposes only. Oxidizing cold pills is illegal, and makes a lousy drug anyway.
After the oxidation/stirring-time has expired and the methcathinone is in solution ready to be extracted, before adding 25% NaOH, add about five milliliters of isopropylalcohol (store bought of any concentration is fine, exact measurements not really needed [ballpark figure is fine]) to the mix. Stir for about ten minutes more (mixture may or may not get warm) and then cool the solution which hasn't changed much in appearance, add a volume of toluene equivalent to the solution, start stirring mixture while in an ice-bath, and add the appropriate amount of base. Stirring should be done for about two minutes only. Allow the layers to separate (the top toluene layer should be cloudy and the bottom chromium solution should be totally green) and do final work-up as usual. Yes, you bet your ass that there is NO SLUDGE! What happens is this: The IPA neutralizes the remaining chromic acid in solution that normally, if based, would form the sludge. But since there is no remaining chromic acid, the only thing that forms is the water soluble basic chromium hydroxide. Two SMOOTH layers will form. All you have to do is separate the bottom one, and you're good to go. Trust me on this one. It took forever to figure out, but it does work. There are a few problems that can arise but only if your starting ephedrine isn't pure. Aside from that, you should have no trouble. Really.
A solution composed of 0.99g of sodium dichromate and 1.33g of concentrated sulfuric acid dissolved in 4.46mL of water is added slowly with stirring to 1.65 g of l-ephedrine dissolved in 4.7mL of water and 0.52mL of concentrated sulfuric acid at room temperature. The mixture is stirred at room temperature for an additional 4-6 hours and then made alkaline with sodium hydroxide solution. The aqueous mixture is extracted with two volumes of chloroform and then with two volumes of ether. The organic extracts containing the free base of l-methcathinone are combined, treated with an excess of dry hydrogen chloride gas and the solvents evaporated. The residual l-methcathinone hydrochloride is stirred with petroleum ether, collected and purified by dissolving in ethanol and reprecipitating with ether; mp 182-184°C.